High methionine, low folate and low vitamin B6/B12 (HM-LF-LV) diet causes neurodegeneration and subsequent short-term memory loss.
High methionine, low folate and low vitamin B6/B12 (HM-LF-LV) diet causes neurodegeneration and subsequent short-term memory loss.
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DOI：
10.1007/s11011-018-0298-z
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发表时间：
2018-12
影响因子：
3.6
通讯作者：
Tyagi N
中科院分区：
文献类型：
--
作者：
Nuru M;Muradashvili N;Kalani A;Lominadze D;Tyagi N
蛋氨酸是一种必需氨基酸，在普通美国人的饮食中含量丰富，如肉类、鱼类和蛋类。过量食用这类食物往往会超出人体对蛋氨酸的正常需求；这被发现与神经退行性疾病的发展有关。然而，蛋氨酸对大脑影响的机制途径尚不清楚。本研究旨在探讨高蛋氨酸、低叶酸和低维生素B6/B12 （lm - lf - lv）饮食对脑内神经元和血管特异性标志物功能障碍的影响。C57BL6/J雄性小鼠（8 ~ 10周龄）饲喂HM-LF-LV日粮6周。通过使用新对象识别测试（NORT）测量短期记忆来确定小鼠的认知功能。通过测定神经元核抗原（NeuN）、神经元特异性烯醇化酶（NSE）和氟玉C（FJC）荧光水平评价神经元功能障碍；同时，通过评估采集脑组织中内皮连接蛋白血管内皮-钙粘蛋白（VE-Cadherin）和Claudin-5的水平来评估脑血管损伤。通过荧光标记白蛋白在体内微血管渗漏来评估脑血管通透性。脑组织内皮和神经元型一氧化氮合酶（eNOS, nNOS）调节和血管炎症（ICAM：细胞间黏附分子）也进行了评估。所有的评估在整个研究期间每隔一周进行一次。NORT显示，与野生型对照组相比，饲喂HM-LF-LV饮食6周的小鼠短期记忆显著降低。我们的实验数据显示，与正常饮食喂养的对照组小鼠相比，HM-LF-LV饮食喂养的小鼠神经元功能障碍（脑内NeuN水平降低和FJC阳性神经元增加）更为突出。在实验小鼠中，与对照组相比，心肌静脉通透性（微血管渗漏）增加，VE-Cadherin表达降低，可见脑血管破坏程度升高。实验小鼠nNOS的轻微下降和eNOS的增加表明，长期饲喂HM-LF-LV日粮有降低神经元发育潜力的趋势。总的来说，我们的研究结果表明，高蛋氨酸、低叶酸和低维生素B6/B12的日粮会导致神经元变性和血管功能障碍增加，从而导致短期记忆丧失。有趣的是，显著的神经元损伤先于血管功能障碍。
Methionine is an essential amino acid found in rich quantities in average American diet such as meats, fish and eggs. Excessive consumption of such food often exceeds the normal requirement of the methionine in our body; which found to be related to the development of neurodegenerative disorders. However, the mechanistic pathways of methionine’s influence on the brain are unclear. The present study is focus on the effects of high methionine, low folate and low vitamin B6/B12 (HM-LF-LV) diet on the dysfunction of neuronal and vascular specific markers in the brain. C57BL6/J male mice (8–10 week old) were fed with HM-LF-LV diet for a 6 week period. Cognitive function of mice was determine by measuring short-term memory using a Novel Object Recognition test (NORT). Neuronal dysfunction were evaluate by measuring the levels of Neuronal nuclear antigen (NeuN), Neuron-specific-enolase (NSE) and Fluoro-jade C(FJC) fluorescence; while cerebrovascular disruption were evaluate by assessing levels of endothelial junction proteins Vascular Endothelial-Cadherin (VE-Cadherin) and Claudin-5 in harvested brain tissue. Cerebrovascular permeability was assess by evaluating microvascular leakage of fluorescently labeled albumin in vivo. Endothelial and Neuronal Nitric Oxide Synthase (eNOS, nNOS) regulation and vascular inflammation (ICAM: intercellular adhesion molecules) were also evaluate in brain tissue. All assessments were conduct at weekly intervals throughout the study duration. NORT showed a significant temporal decrease in short-term memory of mice fed on HM-LF-LV diet for 6 weeks compared to the wild-type control group. Our experimental data showed that neuronal dysfunction (decreased NeuN levels and increased FJC positive neurons in brain) was more prominent in HM-LF-LV diet fed mice compared to normal diet fed control mice. In experimental mice, cerebrovascular disruption was found to be elevated as evident from increased pial venular permeability (microvascular leakage) and decreased in VE-Cadherin expression compared to control. Slight decrease in nNOS and increase in eNOS in experimental mice suggest a trend towards the decrease in potential for neuronal development due to the long-term HM-LF-LV diet fed. Collectively, our results suggest that a diet containing high methionine, low folate and low vitamin B6/B12 results in increased neuronal degeneration and vascular dysfunction, leading to short-term memory loss. Interestingly, significant neuronal damage precedes vascular dysfunction.
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硫化氢可减轻小鼠中脑内施用的同型半胱氨酸诱导的神经变性和神经血管功能障碍。
影响因子：
3.3
作者：
Kamat PK;Kalani A;Givvimani S;Sathnur PB;Tyagi SC;Tyagi N
通讯作者：
Tyagi N
影响因子：
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作者：
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DOI：
10.1016/j.bbadis.2015.11.015
发表时间：
2016-05
期刊：
Biochimica et biophysica acta
影响因子：
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作者：
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通讯作者：
Wilcock DM
影响因子：
14.8
作者：
Leger, Marianne;Quiedeville, Anne;Freret, Thomas
通讯作者：
Freret, Thomas
影响因子：
6.3
作者：
Kalani, Anuradha;Kamat, Pradip K.;Tyagi, Neetu
通讯作者：
Tyagi, Neetu